Leukocyte common Antigen-Related Protein Tyrosine Phosphatase, PTP-LAR, or LAR protein, also known as protein tyrosine phosphatase, receptor type, F, PTPRF, plays an important role in mammary gland development (Schaapveld et al. (1997) Dev. Biol. 188: 134-146) and in breast cancer tumorigenesis (Freiss et al. (2004) Critical Reviews in Oncology/Hematology. 52: 9-17). It has been demonstrated, inter alia, that the expression of the LAR protein is increased in breast cancer cells, in particular breast cancer cells transformed with the ErbB-2 oncogene (Yang et al. (1999) Mol. Carcinog. 25: 139-149; LeVea et al. (2000) Breast Cancer Research and Treatment 64: 221-228). Furthermore, it would appear that the LAR protein is important for regulating the activity of several tyrosine kinase receptors (Kulas et al. (1996) J Biol Chem 271: 748-754). The LAR protein can also serve as a biomarker for predicting the response to anti-EGFR treatments for breast cancer (WO 2009/021684).
In addition, this protein is a known inhibitor of insulin activation pathways and an increased level of expression of this protein has been found in the insulin-sensitive tissues of obese individuals and insulin-resistant individuals (Ahmad et al. (1995) J Clin Invest 95: 2806-2812). Thus, it has been demonstrated that the LAR protein can contribute to pathological conditions associated with insulin resistance, such as coronary artery disease in patients suffering from type 2 diabetes (Menzaghi et al. (2008) J Intern Med 263: 653-654).
The LAR protein ligands identified to date, essentially of immunoglobulin type, have limitations, in particular in terms of synthesis cost, immunogenicity or affinity for their target.